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Cytokine production was studied in thyroid tissue from patients with Graves' disease. Hashimoto's thyroiditis and non-loxic goitre. The expression of interferon γ tumour necrosis factor α and β interleukin-1α and β, interleukin-6 and platelet-derived growth factor A chain was assessed by slot-blot analysis of the respective mRNA in freshly isolated tissue samples. All seven cytokines were detected in patients of all groups. Although the respective mRNA levels were, in general, higher in thyroid autoimmune disorders, this appeared to relate to the degree of the lymphocytic infiltration of the thyroid gland at the time of surgery. Purified thyroid follicular cells expressed high levels of interleukin-1α and interleukin-6 mRNA and when established in primary culture, purified thyroid follicular cells from Graves' disease as well as non-toxic goitre produced interleukin-1α and interleukin-6 bioactivity spontaneously. In the case of interleukin-1 this could be further augmented by addition of lipopolysaccharide to the thyroid follicular cell cultures. These results demonstrate that the lymphocytic infiltrate found in autoimmune and non-autoimmune thyroid disorders is associated with cytokine production. Additionally we have shown that intrathyroidal cytokine production is not restricted to thyroid-infiltrating mononuclear cells, but may also involve thyroid follicular cells both in vivo and in vitro. The cytokines produced by thyroid follicular cells may have an important role in stimulating autoantigen specific T cells in vitro as both interleukin-1 and interleukin-6 facilitate T cell activation. [ABSTRACT FROM AUTHOR]

In rheumatoid arthritis there is a chronic immune and inflammatory reaction which can lead to the destruction of the diseased joint. Cytokine gene expression was studied in synovial cells using cDNA probes specific for human interleukin I (IL-I), -α and IL-1β, tumour necrosis factor (TNE), -α and TNE β (lymphotoxin); protein molecules which induce cartilage degradation and bone resorption. In all cases studied, IL-I mRNA was present in freshly isolated synovial cells from fluid or membrane. Compared to levels of IL-1 mRNA found in optimally activated normal blood mononuclear cells, the levels of IL-l α mRNA were high in seven of the nine patients studied, whereas IL-lβ mRNA, the dominant form in blood, was relatively lower. TNFα and TNE β mRNA were also detected. Rheumatoid synovial cells, cultured without any stimulus, continued to express high levels of TL-la mRNA for up to 5 days, compared to the 24 h response of activated blood cells; IL-lβ mRNA in culture was also prolonged. Cultures of rheumatoid joint cells produced IL-1 bioactivity, with roughly equal amounts of IL-1 α and β as assessed using neutralizing antibodies. TNF bioactivity was also detected which may be of importance as TNF induces the production of IL-1. The finding of these mediators produced in large amounts in active rheumatoid synovial cells suggests that mutually stimulatory cell interactions, mediated by these molecules, may be important in the chronic inflammation and tissue destruction in rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

to detect immune mediators in RA synovial fluids by bioassay or radioimmunoassay have yielded conflicting results, and so we have begun to analyse the complex immunological reactions occurring within the rheumatoid joint using recombinant DNA technology. High levels of lnterleukin-2 (IL-2) and IL-2 receptor transcripts were found in the mononuclear cells of the rheumatoid lesions. Interferonγ (IFNγ) mRNA was also detected, although al lower level than IL-2. To investigate the possible relevance of IL-2 and IL-2 receptor mRNA expression lo the chronicity of the disease, RA joint cells were cultured in the absence of any stimulus, and the duration of mRNA expression compared to that of blood mononuclear cells (PBM), optimally stimulated. IL-2 mRNA was found to persist in culture for many days, in contrast to its transient (< 24 h) presence in stimulated PBM, IL-2 receptor expression was also prolonged. In contrast IFNγ mRNA, present at biopsy in 10/12 RA samples, was found to increase significantly in vitro. These results suggest that persistent T cell activation is of importance in the pathogenesis of RA, and suggests that prolonged mediator production (IL-2 and IFNγ) may be of importance. The elevation of IFNγ mRNA in culture and its lower relative expression suggests that there are inhibitory immunoregulatory influences within the RA joint. To determine whether abnormal IL-2 mRNA expression may be due to a genetic defect in the region controlling IL-2 gene expression. Southern blotting analysis of genomic DNA was performed with a 5' flanking probe using normal, RA and systemic lupus erythematosis patients. No abnormalities were detected. [ABSTRACT FROM AUTHOR]

This study examines the expression of mRNA for the Th2 cytokine, interleukin-4 (IL-4). Peripheral blood mononuclear cells from deer infected with Mycobacterium boris or vaccinated with live or killed M. bovis bacillus Calmette-Guérin (BCG) were cultured with mycobacterial antigens. IL-4 mRNA production was assayed using the polymerase chain reaction. Elevated levels of IL-4 mRNA were detected in response to at least one antigen preparation in all animals infected with M. bovis as compared with none of the non-infected control animals. After a primary immunization, elevated levels of IL-4 mRNA were detected in only a proportion of vaccinated animals and this did not correlate with whether the vaccine was live BCG or killed BCG in oil. After boosting, all the animals vaccinated with killed BCG in oil exhibited elevated IL-4 mRNA production whereas none of the animals vaccinated with live BCG showed elevated levels. The data suggest that IL-4 is turned off during the immune response to live BCG, that boosting of low-dose live BCG vaccine may be required to ‘imprint’ this signal and that this may be important in the development of protective immunity to tuberculosis. Killed BCG in adjuvant is not protective and as with experimental infection with virulent M. bovis it failed to switch off the IL-4 response. IL-4 may be useful as a diagnostic tool and as an in vitro marker of vaccine efficacy. [ABSTRACT FROM AUTHOR]

The theory developed earlier to describe the averaged diurnal wave of bare soil temperature for a many-day interval is extended to single-day variation. This gives a new analytic model for the soil thermal 'weather'(as opposed to 'climate') under typical temperate seedbed conditions, with input meteorological data in standard time-series form. The model incorporates (i) a 'ramp' term to account for overall linear ascent or descent (i.e. non-cyclic change) in the surface temperature, TO; and (ii) the actual initial condition, θ(z), of the temperature profile, which expresses its effect through a transient term. Soil temperature T(z, t) thus has three distinct components-periodic, ramp, and transient. The model is tested against data from a field site for I day each in spring and autumn. [ABSTRACT FROM AUTHOR]

The energy balance equation for the soil-air interface is expressed, by suitable approximations, in a form linear in the surface temperature T0. This forms the basis of two predictive models for the diurnal variation of T0, averaged over a many-day interval, for potentially evaporating bare soil. Input data include total solar radiation, air temperature and vapour pressure, windspeed ua, cloud cover c, and soil radiative, aerodynamic and thermal properties (the latter assumed uniform). In the simpler model, based on harmonic analysis, ua and c are assumed constant. For Nt observations per day, an algebraic solution is found as a set of equations for the parameters of up to the first Nt/2 harmonics. In the second model, dynamic wind-speed is introduced, and a more complicated linear algebraic method of solution is required. The models have agroclimatic value, since by averaging they predict the thermal 'climate' of soil, in contrast to instantaneous models which describe the time-specific thermal 'weather'. [ABSTRACT FROM AUTHOR]

Two agroclimatic models described earlier are tested against measurements of temperature at the soil surface, T0, and in bulk soil, T( z,t), at an experimental site near Aberdeen during spring, summer and autumn. Soil temperature is predicted most accurately in spring and autumn, when the constant-windspeed model ENBL1 predicts the mean within 0.3 K of measurement. Thedynamic-windspeed model ENBL2 predicts within 0.1 K in all intervals, and with error<0.3 K to depth z=32 cm in spring and autumn. A sensitivity analysis of the output diurnal wave, T0( t), shows that maximum input economy requires only time-dependent shortwave radiation, Rs( t), and air temperature, Ta( t), other inputs being constant. Two or three harmonics in ENBL1 should suffice, requiring four or six measurements per day, depending mainly on the time-structure of the primary driving function Rs. [ABSTRACT FROM AUTHOR]

Iain Small reports on new asthma guidelines which provide the most upto-date review of evidence in asthma care and make recommendations that will alter prescribing and treatments patterns. [ABSTRACT FROM AUTHOR]